CN115023244A

CN115023244A - Antimicrobial articles

Info

Publication number: CN115023244A
Application number: CN202080082272.4A
Authority: CN
Inventors: 戴明华; 刘杰; 约瑟夫·C·斯帕尼奥拉; 斯蒂芬·A·O·奥尔森; 余大华; 刘军钪; 张蕾
Original assignee: 3M Innovative Properties Co
Current assignee: Shuwanuo Intellectual Property Co
Priority date: 2019-12-09
Filing date: 2020-12-04
Publication date: 2022-09-06
Also published as: WO2021116861A1; EP4072604B1; EP4072604B8; EP4072604A1; US20230166000A1

Abstract

An article is disclosed. The article includes a substrate, wherein the substrate has two opposing major surfaces; and particles coated with a metal oxide on the substrate: coating the substrate with particles of a metal; wherein the coated particles are randomly distributed on or in the substrate; and wherein at least some of the coated particles are discrete particles.

Description

Antimicrobial articles

Background

The risk of infection by medical devices is particularly high in the medical field. Antimicrobial articles or coatings are widely used in the medical community to prevent/reduce infection. For example, medical devices used by physicians, including orthopedic needles, compression plates and implants, wound dressings, and the like, must be constantly protected from infection. Metal ions with antimicrobial properties such as Ag, Au, Pt, Pd, Ir, Cu, Sn, Sb, Bi and Zn are used as antimicrobial compounds. Among these metal ions, silver is well known for its highly potent biological activity, and various silver salts, complexes and colloids have been used greatly in medical devices to prevent and control infection.

Disclosure of Invention

While soluble salts of silver have been currently used to prevent microbial infection, they do not provide long-lasting release of silver ions due to losses caused by removal or complexation of free silver ions. They must be reapplied periodically to address this problem. Often reapplication is burdensome or even impractical, such as when an implanted medical device is involved. Accordingly, it is desirable for the antimicrobial article to provide a more effective and sustained release of the antimicrobial agent.

In various exemplary embodiments described herein, the disclosed articles can be used to prevent microbial infection. The disclosed articles can be used to provide enhanced release of antimicrobial agents and thus provide enhanced antimicrobial activity.

In one aspect, the present disclosure provides an article comprising a substrate, wherein the substrate has two opposing major surfaces; and particles coated with a metal oxide on the substrate; coating metal particles on a substrate; wherein the coated particles are randomly distributed on or in the substrate; and wherein at least some of the coated particles are discrete particles.

Other features and aspects of the present disclosure will become apparent by consideration of the detailed description.

Drawings

The present disclosure may be more completely understood in consideration of the following detailed description of various embodiments of the disclosure in connection with the accompanying drawings, in which it should be understood by those of ordinary skill in the art that the drawings illustrate certain exemplary embodiments only, and are not intended to limit the broader aspects of the disclosure.

Fig. 1 is a cross-sectional view of an embodiment of an antimicrobial article of the present disclosure.

Fig. 2 is a cross-sectional view of an embodiment of an antimicrobial article of the present disclosure.

Detailed Description

In the following description, reference is made to the accompanying set of drawings which form a part hereof, and in which is shown by way of illustration several specific embodiments. It is to be understood that other embodiments are contemplated and may be made without departing from the scope or spirit of the present invention. The following detailed description is, therefore, not to be taken in a limiting sense.

Unless otherwise indicated, all numbers expressing feature sizes, amounts, and physical characteristics used in the specification and claims are to be understood as being modified in all instances by the term "about". Accordingly, unless indicated to the contrary, the numerical parameters set forth in the foregoing specification and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by those skilled in the art utilizing the teachings disclosed herein. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claimed embodiments, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Moreover, the use of numerical ranges with endpoints includes all numbers within that range (e.g., 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, and 5), as well as any narrower range or single value within that range.

Various exemplary embodiments of the present disclosure will now be described with particular reference to the accompanying drawings. Various modifications and alterations may be made to the exemplary embodiments of the present disclosure without departing from the spirit and scope thereof. Accordingly, it is to be understood that the embodiments of the present disclosure are not to be limited to the exemplary embodiments described below, but are to be controlled by the limitations set forth in the claims and any equivalents thereof.

An article is disclosed. Fig. 1 is a cross-sectional view of an embodiment of an article 1. In summary, the article 1 includes a substrate 10 having two opposing

major surfaces

12 and 14. The article 1 includes particles 20 coated with a metal oxide 22 on a substrate 10. The article 1 includes particles 30 coated with a metal 32 on a substrate 10. In the embodiment shown in fig. 1, particles 20 and particles 30 are on the same opposing major surfaces. Alternatively, particles 20 and particles 30 may be on different opposing major surfaces, such as particles 20 coated with a metal oxide on major surface 12 and particles 30 coated with a metal on major surface 14. The coated

particles

20 and 30 may be randomly distributed on or in the substrate. In some embodiments, at least some of the coated

particles

20 and 30 are discrete particles. In some embodiments, all of the coated

particles

20 and 30 are discrete particles. In some embodiments, the article may further comprise a release liner covering the coated particles.

In some embodiments, the surface of the substrate is partially covered by the particles such that the substrate surface is partially exposed. In some embodiments, 2% to 95% of the surface area of the substrate is not covered by particles. In some embodiments, 20% to 80% of the surface area of the substrate is not covered by particles. In some embodiments, 2% to 50% of the surface area of the substrate is not covered by particles. In some embodiments, 2% to 30% of the surface area of the substrate is not covered by particles.

In some embodiments, at least 5% of the surface area of the substrate is covered by the particles. In some embodiments, at least 10% of the surface area of the substrate is covered by the particles. In some embodiments, at least 20% of the surface area of the substrate is covered by the particles. In some embodiments, at least 40% of the surface area of the substrate is covered by the particles. In some embodiments, at least 50% of the surface area of the substrate is covered by the particles. In some embodiments, at least 70% of the surface area of the substrate is covered by the particles. In some embodiments, at least 85% of the surface area of the substrate is covered by the particles.

In some embodiments, no more than 98% of the surface area of the substrate is covered by particles. In some embodiments, no more than 95% of the surface area of the substrate is covered by particles. In some embodiments, no more than 90% of the surface area of the substrate is covered by particles. In some embodiments, no more than 85% of the surface area of the substrate is covered by particles. In some embodiments, no more than 70% of the surface area of the substrate is covered by particles. In some embodiments, no more than 50% of the surface area of the substrate is covered by particles. In some embodiments, no more than 40% of the surface area of the substrate is covered by particles. In some embodiments, no more than 30% of the surface area of the substrate is covered by particles.

The articles of the present disclosure can be used to provide antimicrobial effects. The article can be provided to a health care provider and can be applied to a subject to release the antimicrobial agent. The articles of the present disclosure provide synergistic antimicrobial functionality to achieve faster contact killing performance with lower silver oxide coatings, e.g., less than 20mg silver oxide/100 cm ² Preferably less than 10mg silver oxide/100 cm ² Or even more preferably less than 5mg silver oxide/100 cm ² 。

In some embodiments, the article comprises less than 20 micrograms/cm ² Less than 10 microgram/cm ² Or less than 5 microgram/cm ² The silver oxide of (3). In some embodiments, the article comprises greater than 2 micrograms/cm ² Silver oxide of (2). In one embodiment, the article comprises from about 2.5 to 15 micrograms/cm ² The silver oxide of (3).

In some embodiments, the article comprises less than 10 micrograms/cm ² Less than 5. mu.g/cm ² Less than 2. mu.g/cm ² Or less than 1 microgram/cm ² The copper of (1). In some embodiments, the article comprises greater than 0.1 micrograms/cm ² The copper of (1). In one embodiment, the article comprises from about 0.15 to 3 micrograms/cm ² The copper of (1).

In some embodiments, the article comprises about 2.5-15 micrograms/cm ² And about 0.2-3 micrograms/cm of silver oxide ² The copper of (1).

In some embodiments, the coated particles may be randomly distributed on or in one or more sections of the substrate. A section of the substrate can be defined as a portion of one major surface having a surface area less than the total surface area of the one major surface. The total surface area of the one major surface may be defined by the outer edge of the substrate. The surface area of a segment may be defined as the surface area of the substrate comprising the distributed particles. In some embodiments, the coated particles are randomly distributed on or in a section of the substrate. In some embodiments, the coated particles are randomly distributed on or in a section of the substrate, and the section of the substrate comprises less than 20 micrograms/cm ² Less than 10 microgram/cm ² Or less than 5 microgram/cm ² Silver oxide of (2). In some embodiments, the coated particles are randomly distributed on or in a section of the substrate, and the section of the substrate comprises greater than 2 micrograms/cm ² Silver oxide of (2). In one embodiment, the segment of the substrate comprises about 2.5 to 15 micrograms/cm ² Silver oxide of (2). In one embodiment, the segment of the substrate comprises about 2.5 to 15 micrograms/cm ² A hydrocolloid polymer of silver oxide.

In some embodiments, the coated particles are randomly distributed on or in a segment of the substrate, and the segment of the substrate comprisesContaining less than 10 microgram/cm ² Less than 5. mu.g/cm ² Less than 2. mu.g/cm ² Or less than 1 microgram/cm ² The copper of (1). In some embodiments, the coated particles are randomly distributed on or in a section of the substrate, and the section of the substrate comprises greater than 0.1 micrograms/cm ² The copper (b). In one embodiment, the segment of the substrate comprises about 0.15 to 3 micrograms/cm ² The copper of (1).

In some embodiments, the coated particles are randomly distributed on or in a section of the substrate, and the section of the substrate comprises about 2.5-10 micrograms/cm ² And about 0.2-3 micrograms/cm of silver oxide ² The copper (b).

In some embodiments, the particles are randomly distributed on or in one or more islands on the substrate. The islands comprise a substrate segment containing particles, which segment is completely surrounded by a substrate segment not containing particles. The island also includes a particle-containing substrate segment surrounded by a particle-free substrate segment and an edge of the substrate or an edge of the article. In some embodiments, the islands comprise about 2.5-10 micrograms/cm ² Silver oxide of (2). In some embodiments, the islands comprise about 0.15 to 3 micrograms/cm ² The copper of (1). In some embodiments, the islands comprise about 2.5-10 micrograms/cm ² And 0.2-3 microgram/cm of silver oxide ² The copper of (1).

In some embodiments, at least one major surface of the substrate comprises about 2.5 to 15 micrograms/cm ² Silver oxide of (2). In some embodiments, at least one surface of the substrate comprises about 0.15 to 3 micrograms/cm ² The copper of (1). In some embodiments, at least one surface of the substrate comprises about 2.5-15 micrograms/cm ² And about 0.2-3 micrograms/cm of silver oxide ² The copper (b).

The particles are typically distributed on the surface of the substrate.

In some embodiments, the coated particles are distributed on one major surface of the substrate and the concentration of silver oxide on one major surface is about 2.5 to 15 micrograms/cm ² . In some embodiments, the coated particles are distributed on one major surface of the substrate, andand the concentration of copper on one major surface is about 0.15 to 3 micrograms/cm ² . In some embodiments, the coated particles are distributed on one major surface of the substrate, wherein the concentration of silver oxide on the major surface is from about 2.5 to 15 micrograms/cm ² And the concentration of copper on the major surface is about 0.15 to 3 micrograms/cm ² . In some embodiments, the coated particles are distributed on one major surface of the substrate, wherein the concentration of silver oxide on the major surface is from about 2.5 to 15 micrograms/cm ² And the concentration of copper on the major surface is about 0.15 to 3 micrograms/cm ² And the substrate is a hydrocolloid polymer.

In some embodiments, the coated particles are distributed on at least one major surface of the substrate and the concentration of silver oxide on the at least one major surface is from about 2.5 to 15 micrograms/cm ² . In some embodiments, the coated particles are distributed on at least one major surface of the substrate, and the concentration of copper on the at least one major surface is from about 0.15 to 3 micrograms/cm ² 。

Base material

The substrate may be selected from the group consisting of foams, meshes, nettings, woven materials, non-woven materials, cotton, cellulosic fabrics, perforated films, hydrocolloids, hydrogels, polymers with inherent porosity, pressure sensitive adhesives and combinations thereof. In some embodiments, the substrate can be an absorbent substrate selected from the group consisting of: foams, meshes, nettings, woven materials, non-woven materials, cotton, cellulosic fabrics, perforated films, hydrocolloids, hydrogels, polymers with inherent porosity, pressure sensitive adhesives, and combinations thereof. Exemplary absorbent substrates may include films, fabrics, or porous articles made from viscose, rayon, alginate yarns, gauze, biopolymers, polyurethanes, biodegradable polymers, or polymers described in U.S. patent No. 7,745,509, the disclosure of which is incorporated herein by reference. The absorbent material used in the absorbent substrate may be made of any suitable material, including but not limited to woven or non-woven cotton or rayon or netting and perforated films made of nylon, polyester or polyolefin. The absorbent pad can be used as an absorbent layer and can be used to contain a variety of substances, optionally including drugs for transdermal administration, chemical indicators for monitoring hormones or other substances in a patient, and the like.

The absorbent layer may comprise a hydrocolloid composition, including those described in U.S. patent nos. 5,622,711 and 5,633,010, the disclosures of which are incorporated herein by reference. The hydrocolloid absorbent may include, for example: natural hydrocolloids such as pectin, gelatin or carboxymethylcellulose (CMC) (Aqualon corp., Wilmington, Del., wil.); semi-synthetic hydrocolloids, such as cross-linked carboxymethylcellulose (X4ink CMC) (e.g., Ac-Di-Sol; FMC Corp., Philadelphia, Pa.), synthetic hydrocolloids, such as cross-linked polyacrylic acid (PAA) (e.g., CARBOPOL. RTM.) ^TM No. 974P; b.f. goodrich, breksville, Ohio), or a combination thereof. The absorbent layer may also be made from other synthetic and natural hydrophilic materials including polymer gels and foams.

In one embodiment, the substrate is a hydrocolloid polymer.

Particles

The particles of the present disclosure may be any suitable particles, such as non-metallic particles. In some embodiments, the particulate material may be an electrical insulator, such as cellulose particles. The cellulose in the particles may be powdered cellulose or may be modified cellulose such as methyl cellulose, cellulose acetate and hydroxypropylmethyl cellulose. The particles may be any suitable plastic particles. For example, polystyrene particles, polyethylene particles, polypropylene particles, PET particles, poly (methyl methacrylate) particles, and polyurethane particles may be used. The plastic particles may be made of natural and/or synthetic polymers. The plastic particles may be made of a single polymer or a blend of polymers.

The particles may be from about 1 micron to about 1000 microns, from about 1 micron to about 500 microns, or from about 1 micron to about 100 microns in size.

The metal oxide used to coat the particles of the present disclosure may be a metal oxide known to have an antimicrobial effect. For most medical uses, the metal oxide may also be biocompatible. In some embodiments, the metal oxides may include, but are not limited to: silver oxide, copper oxide, gold oxide, zinc oxide, magnesium oxide, titanium oxide, chromium oxide, and combinations thereof. In some of these embodiments, the metal oxide may be silver oxide, including but not limited to Ag _X Oy, x-2 and y-1 or x-y-4. In some embodiments, the metal oxide is Ag ₂ O。

The particles may be coated by the metal oxide by any suitable means, for example by physical vapour deposition techniques. Physical vapor deposition techniques may include, but are not limited to, vacuum or arc evaporation, sputtering, magnetron sputtering, and ion plating methods. Suitable physical vapor deposition techniques may include those described in U.S. patent 4,364,995; 5,681,575, and 5,753,251, the disclosures of which are incorporated herein by reference.

For metal oxide coating by controlled introduction of reactive materials, such as oxygen, into the metal vapor stream of the vapor deposition apparatus during vapor deposition of the metal onto the particles, controlled conversion of the metal to metal oxide can be achieved. Thus, by controlling the amount of reactive vapor or gas introduced, the ratio of metal to metal oxide in the metal oxide layer can be controlled. For 100% conversion of metal to metal oxide at a given level of the layer, at least a stoichiometric amount of an oxygen-containing gas or steam is introduced into a portion of the metal vapor stream. As the amount of oxygen-containing gas is increased, the metal oxide layer will contain a higher weight percentage of metal oxide. The ability to achieve sustainable release of metal atoms, ions, molecules or clusters can be influenced by varying the amount of oxygen-containing gas. As the content of the introduced oxygen-containing gas increases, the metal ions released from the article subsequently increase as the amount of metal oxide increases. Thus, a higher weight percentage of metal oxide, for example, can provide enhanced release of antimicrobial agents such as metal ions and provide increased antimicrobial activity.

The metal oxide may be formed as a thin film. The film can have a thickness no greater than that required to sustainably provide release of the metal ions over a suitable period of time. In this regard, the thickness will vary with the particular metal in the coating (which changes solubility and abrasion resistance), and with the amount of oxygen-containing gas or steam introduced to the metal vapor stream. The thickness will be sufficiently thin that the metal oxide layer does not interfere with dimensional tolerances or flexibility of the article for its intended use. Typically, the metal oxide layer is less than 1 micron thick. However, it will be appreciated that increased thickness may be used depending on the extent of release of metal ions required over a period of time.

The metal coating the particles of the present disclosure may be a metal known to have a positive potential. In some embodiments, the metal may include, but is not limited to, zinc, magnesium, aluminum, iron, calcium, tin, copper, titanium, chromium, nickel, and alloys thereof.

The particles may be formed from the metal by any suitable means, for example by vapour deposition techniques. Vapor deposition techniques may include, but are not limited to, vacuum or arc evaporation, sputtering, magnetron sputtering, and ion plating methods. Suitable physical vapor deposition techniques may include those described in U.S. patent 4,364,995; 5,681,575 and 5,753,251, the disclosures of which are incorporated herein by reference.

The metal may be formed as a thin film. The film can have a thickness no greater than that required to sustainably provide release of the metal ions over a suitable period of time. In this regard, the thickness will vary with the particular metal in the coating (which changes solubility and abrasion resistance), and with the amount of oxygen-containing gas or steam introduced to the metal vapor stream. The thickness will be sufficiently thin that the metal layer does not interfere with the dimensional tolerances or flexibility of the article for its intended utility. Typically, the metal layer is less than 1 micron thick. However, it will be appreciated that increased thickness may be used depending on the extent of release of metal ions required over a period of time.

In some embodiments, the article has a metal oxide to metal ratio of 10:1 to 1:10, 9:1 to 1:9, 8:1 to 1:8, 7:1 to 1:7, 6:1 to 1:6, 5:1 to 1:5, 4:1 to 1:4, 3:1 to 1:3, or 2:1 to 1: 2. In some embodiments, the article has a metal oxide to metal ratio of 5: 1.

The metal oxide and/or metal coated particles may be fully coated or partially coated. In the embodiment shown in fig. 1, particles 20 are completely coated with metal oxide 22 and particles 30 are completely coated with metal 32. In some embodiments shown in fig. 2, the surface of a particle 20 or a particle 30 is partially covered with a metal oxide 22 or a metal 32, such that the particle surface is partially exposed. Partially coated particles comprise coated regions and uncoated regions on the surface of the particle. In some embodiments, at least some of the metal oxide coated particles are partially coated. In some embodiments, at least some of the metal-coated particles are partially coated.

For partially coated particles, at least some of the particle surfaces are exposed. In some embodiments, at least 5%, 10%, 20%, 30%, 50%, or 70% of the particle surface is exposed (i.e., uncoated). In some embodiments, no more than 95%, 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, or 10% of the particle surface is exposed (i.e., uncoated).

In some embodiments, the article comprises partially coated particles having at least 10% of the particle surface exposed (i.e., uncoated). In some embodiments, the article comprises partially coated particles having at least 20% of the particle surface exposed (i.e., uncoated). In some embodiments, the article comprises partially coated particles having at least 30% of the particle surface exposed (i.e., uncoated). In some embodiments, the article comprises partially coated particles having at least 50% of the particle surface exposed (i.e., uncoated).

In some embodiments, the exposed particle surface is cellulose or modified cellulose. In some embodiments, the exposed particle surface is a polymer that acts as an electrical insulator.

In some embodiments, the article comprises partially coated particles having at least 10% of the coated particle surface. In some embodiments, the article comprises partially coated particles having at least 20% of the coated particle surface. In some embodiments, the article comprises partially coated particles having at least 30% of the surface of the coated particles. In some embodiments, the article comprises partially coated particles having at least 50% of the coated particle surface. In some embodiments, the article comprises partially coated particles having at least 75% of the coated particle surface. In some embodiments, the article comprises partially coated particles having at least 85% of the coated particle surface.

In some embodiments, the article comprises partially coated particles having no more than 95%, 90%, 85%, or 75% of the coated particle surface. In some embodiments, the article comprises partially coated particles having no more than 90% of the coated particle surface.

In some embodiments, the partially coated particles are metal oxide coated particles. In some embodiments, the partially coated particles are silver oxide coated particles. In some embodiments, the partially coated particles are metal coated particles. In some embodiments, the partially coated particles are coated particles.

Optional Components

Suitable release liners may be made of kraft paper, polyethylene, polypropylene, polyester or composites of any of these materials. In one embodiment, a package containing an adhesive dressing may be used as a release liner. In one embodiment, the liner is coated with a release agent such as a fluorochemical or silicone. For example, U.S. Pat. No. 4,472,480, whose disclosure is incorporated herein by reference, describes low surface energy perfluorochemical gaskets. In one embodiment, the liner is a paper, polyolefin film, or polyester film coated with a silicone release material.

Characteristics of

The article can generate at least one electrical current when introduced to the electrolyte solution. In some embodiments, the article is capable of generating an electrical current in the range of about 10 μ Α to about 5000 μ Α when introduced into an electrolytic solution. In some embodiments, the article is capable of generating an electrical current in the range of about 100 μ Α to about 1000 μ Α when introduced into an electrolytic solution. In the presence of the conductive solution, a redox reaction may occur, and thus a current may be generated between the metal oxide layer and the metal layer. For example, when the metal oxide layer contains silver oxide and the metal layer contains zinc, the silver oxide is a cathode (positive electrode) and the zinc is an anode (negative electrode) due to the inflow of electrons from the zinc to the silver oxide. The flow of ions generates a current. Thus, when the article of the present application is used as a wound dressing, it can regenerate physiological currents, which are important for the induction of neutrophils, macrophages and fibroblasts necessary for the healing process. In addition, the current may stimulate regional nerve endings to promote their involvement in wound elimination. In addition, the current may inhibit bacterial growth. Thus, the electric current generated by the article can have a synergistic antimicrobial function as well as Ag from the article ⁺ And (4) releasing.

The article may produce a pH of greater than 6.2, greater than 6.5, greater than 7, greater than 8, greater than 9 when contacted with water. Without being bound by theory, the higher pH level generated when the article is contacted with water may enhance the antimicrobial function of the article.

Various exemplary embodiments of the present disclosure are further illustrated by the following list of embodiments, which should not be construed to unduly limit the present disclosure:

detailed description of the preferred embodiments

Embodiment 1 is an article comprising a substrate, wherein the substrate has two opposing major surfaces; and particles coated with a metal oxide on the substrate; coating metal particles on a substrate; wherein the coated particles are randomly distributed on or in the substrate; and wherein at least some of the coated particles are discrete particles.

Embodiment 2 is the article of embodiment 1, wherein the metal oxide is selected from the group consisting of silver oxide, copper oxide, platinum oxide, zinc oxide, magnesium oxide, titanium oxide, chromium oxide, and combinations thereof.

Embodiment 3 is the article of any one of embodiments 1 to 2, wherein the metal oxide is silver oxide.

Embodiment 4 is the article of any of embodiments 3, wherein the silver oxide is Ag _X Oy, x-2 and y-1 or x-y-4.

Embodiment 5 is the article of any one of embodiments 1 to 4, wherein the metal is selected from zinc, magnesium, aluminum, iron, calcium, tin, copper, titanium, chromium, nickel, and alloys thereof.

Embodiment 6 is the article of any of embodiments 1-5, wherein the ratio of metal oxide to metal is 10:1 to 1: 10.

Embodiment 7 is the article of any one of embodiments 1 to 6, wherein the ratio of metal oxide to metal is 5: 1.

Embodiment 8 is the article of any of embodiments 1 to 7, further comprising a release liner covering the coated particles.

Embodiment 9 is the article of any one of embodiments 1 to 8, wherein the article is capable of generating an electrical current in a range of about 1 μ Α to about 5000 μ Α when introduced into an electrolytic solution.

Embodiment 10 is the article of any one of embodiments 1-9, wherein the article is capable of generating an electrical current in a range of about 100 μ Α to about 1000 μ Α when introduced into an electrolytic solution.

Embodiment 11 is the article of any of embodiments 1-10, wherein the substrate is selected from the group consisting of foams, meshes, nettings, woven materials, non-woven materials, cotton, cellulosic fabrics, perforated films, hydrocolloids, hydrogels, polymers with intrinsic porosity, pressure sensitive adhesives, and combinations thereof.

Embodiment 12 is the article of any of embodiments 1 to 11, wherein the article is an antimicrobial article.

Embodiment 13 is the article of any one of embodiments 1 to 12, wherein the article is an antimicrobial article for treating acne.

Embodiment 14 is the article of any one of embodiments 1 to 13, wherein all of the coated particles are discrete particles.

Embodiment 15 is the article of any one of embodiments 1 to 14, wherein the particles are non-metallic particles.

Embodiment 16 is the article of any one of embodiments 1 to 15, wherein the metal oxide coated particles are partially coated with metal oxide.

Embodiment 17 is the article of any one of embodiments 1 to 16, wherein the metal-coated particles are partially metal-coated.

Embodiment 18 is the article of any one of embodiments 1 to 17, wherein a surface portion of the substrate is covered with particles.

Embodiment 19 is the article of any one of embodiments 1 to 18, wherein from 2% to 95% of the surface area of the substrate is not covered by particles.

Embodiment 20 is the article of any one of embodiments 1 to 19, wherein from 2% to 50% of the surface area of the substrate is not covered by particles.

Examples

These examples are for illustrative purposes only and are not intended to unduly limit the scope of the appended claims. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the disclosure are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.

Preparation of copper-coated particles by physical vapor deposition

The (hydroxypropyl) methylcellulose particles (product No. H7509, obtained from Sigma Aldrich Corporation of st.louis, MO, st.) were placed in a 100 ℃ oven for greater than 24 hours to remove excess water. The dried particles (14.94g) were loaded into a 40mL paddle drum particle blender (equipment design, as described in fig. 2 and 3 of U.S. patent No. 8,664,149, the disclosure of which is incorporated herein by reference). The stirrer was positioned in the sputtering vacuum chamber and the chamber was evacuated to 5.6x10 ^-6 Base pressure of torr. A 3 inch (7.62cm) diameter x0.25 inch (0.63cm) copper sputtering target (99.999% pure Kurt J leischer Company, Jefferson Hills, PA) was used as the copper material source and the process pressure was 10 millitorr. After the base pressure was reached, a 100sccm (standard cubic centimeter per minute) argon gas was flowed into the vacuum chamber and directly into the particle stirrer. The paddle drum was rotated at 6rpm (rev/min) and copper was deposited on the substrate by a 0.1kW DC sputtering process for 1 hour 36 minutes (467 volts). Based on the amount of copper removed from the target and the process efficiency of the apparatus, 0.6 wt% copper coating was deposited on the particles.

Preparation of silver oxide coated particles by physical vapor deposition

The (hydroxypropyl) methylcellulose particles (product No. H7509, obtained from sigma aldrich) were placed in a 100 ℃ oven for greater than 24 hours to remove excess water. The dried particles (15.49g) were loaded into a 40mL paddle drum particle stirrer (equipment design as described in fig. 2 and 3 of U.S. patent No. 8,664,149). The stirrer was positioned in the sputtering vacuum chamber and the chamber was evacuated to 2.5x10 ^-6 Base pressure of torr. A 3 inch (7.62cm) diameter x0.25 inch (0.63cm) thick silver sputtering target (99.99% purity, coulter J leisco) was used as the silver material source and the process pressure was 10 millitorr. After the base pressure was reached, 90sccm argon/10 sccm oxygen was flowed into the vacuum chamber and directly into the particle stirrer. The paddle drum was rotated at 6rpm and silver was deposited on the substrate by a 0.1kW DC sputtering process for 6 hours 36 minutes (501 volts). Based on slave targetsWith the amount of silver removed and the process efficiency of the equipment, a 6.0 wt% silver oxide coating was deposited on the particles.

EXAMPLE 1 preparation of articles

Articles were prepared using 3cm x 3cm sections cut from TEGADERM hydrocolloid dressing #90002 (3M Corporation, Maplewood, MN) of meprolid, MN) as the base material for the substrate. The silver oxide coated particles and the copper coated particles are mixed together to form a mixed particle distribution. The release liner was removed from each section of the dressing and a measured amount of the mixture of coated particles was sprayed evenly onto the surface of the release liner. The hydrocolloid sheet is then placed on the release liner such that the particles are sandwiched between the release liner surface and the hydrocolloid surface. The particles were adhered to the surface of the hydrocolloid substrate using pressure from a hand press roller. The roller is rolled back and forth several times over the surface of the release liner. The release liner is then removed to provide the final article. Preparation of formulations containing different concentrations (micrograms/cm) by adjusting the amount and ratio of particles added to the surface of the article ² ) Silver oxide and copper. Comparative articles comprising only silver oxide coated particles or only copper coated particles were prepared. Control articles comprising the hydrocolloid substrate without any silver oxide-coated particles or copper-coated particles were also prepared. Preparations A-B and comparative preparations A-D are described in Table 1.

Example 2 testing of articles for antimicrobial Activity

The antibacterial Activity of the articles was evaluated using Test Method ASTM E2180-18 (Standard Test Method for Determining the Activity of Incorporated antimicrobials in Polymeric or Hydrophobic Materials). Propionibacterium acnes (Propionibacterium acnes/P.acnes) ATCC 6919 was obtained from ATCC (Manassas, Va.). A single colony of Propionibacterium acnes from a stock agar culture was inoculated into Oxoid anaerobic substrate broth (Oakohyde Co., Becton Stoke, England)(Oxoid Limited, Basingstoke, UK)) and incubated at 37 ℃ for 18 hours to provide 1-10X 10 of Propionibacterium acnes ⁸ cfu/mL culture.

An agar slurry was prepared by dissolving 0.85g NaCl and 0.3g agar (Teknova Incorporated, Hollister, Calif.) in 100mL deionized water. The slurry was heated on a hot plate with stirring until the agar dissolved. The agar slurry was sterilized in an autoclave (set at 121 ℃, 15psi) for 15 minutes and then equilibrated to 45 ℃. Culturing Propionibacterium acnes (1-10X 10) ⁸ cfu/mL) was centrifuged (300rpm for 5 minutes) to form a cell pellet. Adding the precipitate to the agar slurry and mixing to produce a concentration of 1-10X 10 in the molten agar slurry ⁶ cfu/mL Propionibacterium acnes.

For each article type, three replicate samples (n-3) were prepared and tested. Each final article (prepared according to example 1) was placed in a sterile 15 x 100mm petri dish with the particle-coated surface exposed. The exposed surface of the article was wetted by gently wiping the surface with a sterile cotton swab immersed in sterile 0.85% saline solution. The molten seed agar slurry (0.2mL) was applied to the wetted surface of the article using a pipette. The slurry is slowly applied at a low angle of incidence relative to the article surface and then spread over the entire surface using a plastic applicator. The agar coated articles were placed in an incubator at 25 ℃ for 3 hours. Each incubated preparation was aseptically transferred to a 50mL sample tube containing 10mL of 1X Phosphate Buffered Saline (PBS) (obtained from the tenuhua company and sterilized by 0.2 micron filtration). The sample tube was placed in a Branson8510 ultrasonic bath (Branson Company, Danbury, CT) and sonicated for one minute. The tubes were then vortexed for one minute using a VWR simulated vortex mixer (VWR International, Radnor, PA) with a mixing speed set at 6 (a speed setting of 1-10). Samples were serially diluted seven times with PBS (10-fold dilution). Aliquots (3 μ l) from the final dilutions were added to Oxoid anaerobe-based agar plates (okoude ltd). The plates were incubated at 37 ℃ for 16 hours. Colonies from each plate were counted by visual inspection. Cfu counts (n-3) for individual plates were averaged and the number of colony forming units per mL (cfu/mL) recovered from the inoculated preparation was calculated (based on serial dilutions) using the average count value. In Table 1, the calculated cfu/mL values are reported.

Table 1.

EXAMPLE 3 preparation and testing of articles

Articles C-G were prepared according to the method of example 1 with a constant silver oxide coating weight (3.33 micrograms/cm) ² ) And different copper coating weights (0.07, 0.21, 0.33, 0.50, or 0.62 micrograms/cm) ² ). The articles were tested for antimicrobial activity by the method of example 2. The results are presented in table 2.

Table 2.

EXAMPLE 4 preparation and testing of articles

Articles H-K were prepared according to the method of example 1 with different silver oxide and copper coating weights. The articles were tested for antimicrobial activity by the method of example 2. The results are presented in table 3.

Table 3.

All references and publications cited herein are expressly incorporated by reference into this disclosure in their entirety. Illustrative embodiments of the invention are discussed herein and reference is made to possible variations within the scope of the invention. For example, features depicted in connection with one exemplary embodiment may be used in connection with other embodiments of the invention. These and other variations and modifications in the invention will be apparent to those skilled in the art without departing from the scope of the invention, and it should be understood that this invention is not limited to the illustrative embodiments set forth herein. Accordingly, the invention is to be limited only by the claims provided below and equivalents thereof.

Claims

1. An article of manufacture, comprising:

a substrate, wherein the substrate has two opposing major surfaces; and

coating particles of a metal oxide on the substrate;

coating particles of a metal on the substrate;

wherein the coated particles are randomly distributed on or in the substrate; and is

Wherein at least some of the coated particles are discrete particles.

2. The article of claim 1 wherein the metal oxide is selected from the group consisting of silver oxide, copper oxide, platinum oxide, zinc oxide, magnesium oxide, titanium oxide, chromium oxide, and combinations thereof.

3. The article of any one of claims 1 to 2, wherein the metal oxide is silver oxide.

4. The article of any one of claims 3, wherein the silver oxide is Ag _X Oy, x-2 and y-1 or x-y-4.

5. The article of any one of claims 1 to 4, wherein the metal is selected from zinc, magnesium, aluminum, iron, calcium, tin, copper, titanium, chromium, nickel, and alloys thereof.

6. The article of any one of claims 1 to 5, wherein the ratio of metal oxide to metal is from 10:1 to 1: 10.

7. The article of any one of claims 1 to 6, wherein the ratio of metal oxide to metal is 5: 1.

8. The article of any one of claims 1 to 7, further comprising a release liner covering the coated particles.

9. The article of any one of claims 1 to 8, wherein the article is capable of generating an electrical current in a range of about 1 μ Α to about 5000 μ Α when introduced into an electrolytic solution.

10. The article of any one of claims 1 to 9, wherein the article is capable of generating an electrical current in a range of about 100 μ Α to about 1000 μ Α when introduced into an electrolytic solution.

11. The article of any one of claims 1 to 10, wherein the substrate is selected from the group consisting of foams, meshes, nettings, woven materials, non-woven materials, cotton, cellulosic fabrics, perforated films, hydrocolloids, hydrogels, polymers with intrinsic porosity, pressure sensitive adhesives, and combinations thereof.

12. The article of any one of claims 1 to 11, wherein the article is an antimicrobial article.

13. The article of any one of claims 1 to 12, wherein the article is an antimicrobial article for treating acne.

14. The article of any one of claims 1 to 13, wherein all coated particles are discrete particles.

15. The article of any one of claims 1 to 14, wherein the particles are non-metallic particles.

16. The article of any one of claims 1 to 15, wherein the particles coated with the metal oxide are partially coated with the metal oxide.

17. The article of any one of claims 1 to 16, wherein the particles coated with the metal are partially coated with the metal.